Key Research on TNBC: Top 5 Picks From SABCS
SAN ANTONIO — While major reports on hormone receptor (HR)–positive breast cancer took center stage at the San Antonio Breast Cancer Symposium (SABCS) 2022, research highlighting new findings in triple-negative breast cancer (TNBC) stood out as well.
Medscape Medical News spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Kevin Kalinsky, MD, a medical oncologist and director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University in Atlanta, about the TNBC data that caught their eye and what the findings could mean for clinical practice.
1. Carboplatin for TNBC
Kalinsky’s first pick was a study on the impact of platinum therapy on long-term TNBC outcomes.
The phase 3 randomized controlled trial, presented in general session (GS) 5-01, explored whether adding carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy for patients with TNBC improved disease-free survival, pathologic complete response, or overall survival.
Overall, 365 patients received carboplatin, and 355 did not. At a median follow-up of 67.6 months, the 5-year disease-free survival rate was 70.6% in the carboplatin group, vs 64.5% in the control arm (hazard ratio [HR], 0.79); the 5-year overall survival was also higher in the carboplatin group (74.0% vs 66.7%; HR, 0.75). Pathologic complete response occurred in 55.2% of carboplatin patients, vs 41.5% of control patients.
“These results are important,” Kalinsky said. “The results of this study suggest that there is a benefit to the TNBC population from being treated with carboplatin.”
Kalinsky cautioned, however, that despite the encouraging results, it remains unclear whether there is a specific biomarker for selecting patients who may derive the most benefit from treatment with carboplatin. “This remains an outstanding question,” he said.
2. Risk of Contralateral Breast Cancer
Women with breast cancer who have germline pathogenic variants in BRCA1, BRCA2, CHEK2, or PALB2 had nearly double the risk of contralateral breast cancer in comparison with patients without those variants, according to recent data presented at the meeting (GS4-04).
Researchers estimated the risk of contralateral breast cancer in women with pathogenic variants in comparison with control patients. They found that having ATM does not increase this risk.
“The reason this study is important is that many women with these mutations want to have a bilateral mastectomy, but thus far, the data have been unclear, and the question is, are they going to benefit from having a bilateral mastectomy?” said Kaklamani. “The results of this study help shine a light on what mutations might warrant a bilateral mastectomy. Most of these patients are going to be triple negative.”
Hal Burstein, MD, also weighed in in a tweet, saying the “data should allow many to avoid prophylactic mastectomy.”
3. Cemiplimab Plus LAG-3 Inhibitor in TNBC
Another session that caught Kalinsky’s attention explored results from the I-SPY2 trial (GS5-03), which evaluated the use of the checkpoint inhibitior cemiplimab in combination with LAG-3 inhibitor REGN3767 for patients with early-stage, high-risk, HER2-negative breast cancer.
Among the 73 patients with HER2-negative disease who received cemiplimab plus REGN3767, 33 had TNBC. The control group included 357 patients with HER2-negative tumors, of whom 156 had TNBC. Overall, the combination of a LAG-3 and anti-PD1 inhibitor resulted in a pathologic complete response rate of 60% for patients with TNBC and 37% for patients with HR-positive disease.
“We know that checkpoint inhibitors benefit patients with TNBC, and there has been a lot of interest in looking beyond checkpoint inhibition,” said Kalinsky, who is a co-investigator on the I-SPY trial. “LAG-3 has been a target of interest, and this is the first study looking in the neoadjuvant setting of giving a LAG-3 inhibitor along with a checkpoint inhibitor.”
4. Efficacy vs Side Effect Profile of Cemiplimab
Taking adverse events of immune checkpoint inhibitors into account is also important. Kalinsky and colleagues presented research on the efficacy as well as the side effect profile associated with cemiplimab (PD11-01) among patients in the I-SPY trial.
Overall, cemiplimab was associated with a higher pathologic complete response rate for patients with TNBC (55%) compared with control patients who received paclitaxel followed by doxorubicin/cyclophosphamide (29%). The rate of immune-related adverse events was higher in the cemiplimab group: hypothyroidism, 3% vs 0%; adrenal insufficiency, 6% vs 0%; hyperthyroid, 8% vs 0%; and thyroiditis, 3% vs 0%. However, only one case of grade 3 adrenal insufficiency occurred in the cemiplimab arm.
“I really think the key takeaway is not just the efficacy that is seen in the HER2-negative population but also what the side effect profile is going to be,” Kalinsky said.
5. Olaparib or Carboplatinum?
Kaklamani highlighted data from the GeparOLA study (GS5-02), which evaluated the efficacy and safety of using olaparib instead of carboplatinum along with paclitaxel as neoadjuvant chemotherapy in early-stage HER2-negative breast cancer.
The results of the study indicate that among patients in the cohort with HER2-negative homologous recombination deficiency tumors — those with a g/tBRCA mutation — the two groups had similar pathologic complete responses. Overall, patients in the olaparib group had more invasive disease-free survival events (15 vs 3), more distant disease-free survival events (11 vs 2), and more deaths (6 vs 1). However, when comparing patients with a g/tBRCA mutation, outcomes were comparable in both arms.
“The majority of these patients were triple negative, and I think the importance here is that this [study] shows us whether we should be adding olaparib in some patients who have a homologous recombination deficiency,” Kaklamani said.
San Antonio Breast Cancer Symposium (SABCS) 2022: General sessions 4-04, 5-01, 5-02, and 5-03 and PD11-01. Presented December 6–9, 2022.
Myles Starr is medical journalist based in New York.
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